A clinical study was undertaken to: 1) confirm observations that tissue culture prolongs allograft survival in man; 2) study of various mechanisms which would possibly explain the above phenomenon; and 3) assess the clinical potential of using tissue cultured skin allografts. Our preliminary observation is that tissue culture does not cause an intact skin organ to survive by altering the immunogenicity of cells. Rather, there is a marked decrease in the total number of cells (fibroblasts) and, most importantly, nearly complete loss of endothelial cells. In standard allografts the initial site of immunologic attack at five to ten days is against the endothelium. This leads to vascular statis, thrombosis, and acute death of the entire skin organ. Following transplantation of tissue cultured skin, recipient immune defense contacts the dermal collagen and the few surviving fibroblasts. Dermal collagen has extremely low antigenicity and appears not to incite rejection. The collagen of the dermis is later replaced by the recipient's collagen. In 25 percent of the grafts the fibroblasts, and possibly the epithelium, were identified by HL-A antigen typing in a biopsy of three months. However, cross reactions of HL-A antigens may have caused a false positive reaction.